Pyrrolo pyrazines preparation

Interest in the synthesis and reactions of pyrrolo[3,4- ]pyrazines is focused on two goals. The first is the development of analogs of zopiclone 256, a hypnotic agent <2001MI27>. Analogs of 256 are typically prepared from pyrazine-2,3-dicarboxylic anhydride (a furo[3,4- ]pyrazine) and a variety of aliphatic or aromatic amines <1996MI26, 1997MI28>. 

Pyrazine-2,3-dicarboxylic acid anhydride (180) serves as the basis for the preparation of a series of pyrrolo[3,4-6]pyrazine derivatives <89JSC233>. Thus, treatment with a series of amino acids yields compounds of the type (181) (Equation (62)). 

Some synthetic approaches to pyrazines relied on metal-assisted reactions. A synthesis of 6-substituted 5H-pyrrolol2,3-bJpyrazines via Pd-catalyzed heteroannulation from W-(3-chloropyrazin-2-yl)methanesulfonamide and alkynes was developed <04TL8087>, and 3- and 5-substituted 2(l//)-pyrazinones were prepared by Suzuki and Heck reactions using 3,5-dichloro-2(l//)-pyrazinones <04TL1885>. An improved synthesis of 6-substituted-5//-pyrrolo 2,3-iiJ-pyrazines via microwave-assisted Pd-catalyzed heteroannulation was developed <04TL8631>, and the reaction of a-diazo-P-keto esters with Boc amino acid amides in the presence of a Rh catalyst gave, after air oxidation, pyrazin-6-ones 111, which were then converted into tetrasubstituted pyrazines 112 <04OL4627>. 

Acylpyrroles (13) have been used in two ways to prepare examples of this ring system. Alkylation of the sodium salt of 13 in ethanol with the a -bromoacetal (14) followed by heating with ammonium acetate in acetic acid provides pyrrolo[l,2-a]pyrazines (15) in 25-50% yields. ° Use of phenacyl bromide in place of the bromoacetal gave the corresponding... 

While examining the strategies for the preparation of molybdenum dithiolene complexes as models for oxidoreductase enzymes, a series of potentially bioactive pentathiepino-pyrrolo[l,2-a]-pyrazine derivatives, 258, was discovered and reported (13CC4343). These pentathiepins fused with bis-heterocychc rings are the result of the reaction between alkynyl-substituted heterocycles 257 with elemental sulfur in the presence of molybdenum 0x0 bis-tetrasulfide. 

Oxidation of a protected ribofuranosyl furfuiyl alcohol gave (56) which was used as a precursor of 2-( -glycosyl)pyrroles and -pyrrolo (1,2-al pyrazines.iii The D-lyxopyranosyl imidazole (57) was prepared by (yclization of a polyol precursor, 112... 

Pictet-Spengler-type reaction of pyrrole-derived amine 1096 and enamines 1097 was used recently for the preparation of pyrrolo[l,2-a]pyrazine derivatives 1098 - a [5+1] approach to the construction of pyrazine ring (Scheme 233) [669],... 

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